International Journal of Cardiology, 31(1992) 23-32 0 1992 Elsevier Science Publishers B.V. All rights reserved 0167-5273/92/$05.00
23
CARD10 01526
Marked alternans of the elevated ST segment during occlusion of the left anterior descending coronary artery in percutaneous transluminal coronary angioplasty: clinical background and electrocardiographic features Hideki Okino, Shin-ichi Arima, Hiroshi Yamaguchi, Shoichiro Nakao and Hiromitsu Tanaka First Department of Internal Medicine, Faculty of Medicine, Kagoshima Utkersity, Kagoshima, Japan
(Received 7 June 1991; revision accepted 7 May 1992)
Okino H, Arima S, Yamaguchi H, Nakao S, Tanaka H. Marked alternans of the elevated ST segment during occlusion of the left anterior descending coronary artery in percutaneous transluminal coronary angioplasty: clinical background and electrocardiographic features. Int J Cardiol 1992;37:23-32. To investigate the clinical background and the electrocardiographic features of marked alternans of the elevated ST segment during coronary angioplasty, we examined 1Zlead electrocardiograms recorded continuously during occlusion of the left anterior descending coronary artery by balloon inflation in 41 patients. The incidence of marked ST alternans was 27% of 41 patients and 15% of 117 balloon occlusions. The incidence decreased progressively from the first to the third occlusion. The time course of ST alternans was determined. Compared with patients without ST alternans, patients with ST alternans had a shorter history of angina, less severe stenosis of the target lesion before coronary angioplasty, more leads showing ST elevation during occlusion, higher ST elevation during occlusion and lower incidence of previous myocardial infarction in the left anterior descending coronary arterial area. ST alternans recorded on the surface electrocardiogram may thus be considered a marker of acute severe and extensive myocardial ischemia. Key words: Acute severe ischemia; Ventricular
arrhythmia; Variant angina; Ca antagonist
Introduction Although alternans of the elevated ST segment in electrocardiography has been observed in
Correspondence to: Hiromitsu Tanaka, M.D., First Department of Internal Medicine, Faculty of Medicine, Kagoshima University. Sakuragaoka 8-3.5-1, Kagoshima City. 890, Japan. Tel. 0992-64-2211, ext. 2137 or 2130.
various conditions [l-13], its occurrence is mostly related to severe myocardial ischemia. Since Hellerstein and Liebow [ll reported that electrical alternans including ST alternans was frequently observed following occlusion of the left anterior descending coronary artery, several investigators [ 14-201 have performed experimental studies on the nature and underlying mechanism of ST alternans induced by severe myocardial ischemia.
24
Clinically, ST alternans has also been observed in variant angina. In 1977, Kleinfeld and Rozanski 1101reported that alternans of the ST segment was found in 8 of 21 patients (38%) of Prinzmetal’s variant angina and that it was an electrocardiographic sign in the surface electrocardiogram reflecting an unstable electrical state of the myocardium. In 1982, Rosanski and Kleinfeld [ll] showed that the occurrence of alternans of the ST segment and T wave frequently heralded the onset of ventricular arrhythmias in Prinzmetal’s angina. Recently, Turitto and El-Sherif [12] demonstrated that alternans of the ST segment represented an index of the severity of ischemia and a precursor of ventricular arrhythmias in variant angina. Percutaneous transluminal coronary angioplasty seems to provide a useful model for studying the effects of acute coronary occlusion by balloon inflation during routine therapeutic intervention. In 1984, Joyal et al. [13] reported that ST-segment alternans was observed during coronary angioplasty in a patient with exertional angina. However, to our knowledge, no systematic study has been made of ST alternans during coronary angioplasty. In the present clinical model, measurement of the duration of balloon inflation, localization of the site of coronary artery occluded by the balloon, angiographic data including coronary anatomy and electrocardiographic data were obtained for the study of ST alternans induced by coronary artery occlusion. The present study was undertaken (1) to delineate the electrocardiographic features of marked ST alternans during balloon occlusion of the left anterior descending coronary artery, and (2) to clarify the clinical background to ST alternans in acute coronary occlusion.
Materials
and Methods
Patients Among 130 consecutive patients who underwent their first angioplasty in our department, we selected 41 consecutive patients in whom the left anterior descending coronary artery was a target
for coronary angioplasty and in whom a significant magnitude of ST elevation was observed during coronary occlusion. ST elevation 12 mm 0.16 s after the beginning of QRS complex was defined to be significant. Patients with the following characteristics were excluded: (1) atria1 fibrillation, (2) acute myocardial infarction, (3) acute coronary occlusion occurring during coronary angioplasty, and (4) right or left bundle branch block. The 41 patients ranged in age from 33 to 78 with a mean of 59 yr. There were 33 males and 8 females. We classified the patients into three groups. Group 1 consisted of 11 patients who showed ST alternans during coronary occlusion. Group 2 consisted of 15 patients without previous myocardial infarction in the left anterior descending coronary arterial area who showed no ST alternans. Group 3 consisted of 15 patients with previous myocardial infarction in the left anterior descending coronary arterial area who showed no ST alternans. None of the Group 1 patients had had previous myocardial infarction in the area. Coronary angioplasty protocol Routine antianginal medication consisting of long-acting nitrates, calcium antagonists (diltiazem 90-120 mg daily or nifedipine 20-40 mg daily) and anti-platelet drugs (aspirin 80 mg daily and dipyridamole 150 mg daily) were continued. Nitroglycerine (0.3-0.5 pg/kg/min) and low molecular weight dextran (100 ml/h) were given by intravenous infusion starting 2 h before the procedure. Immediately before control coronary angiography, heparin (10,000 units) was administered intravenously and isosorbide dinitrate (2.55.0 mg> was selectively injected into the coronary artery as a bolus. Coronary angioplasty was performed from the femoral approach using the standard technique. Dilatation was performed with an appropriately sized Simpson-Robert dilatation balloon catheter (ACS) for 60-130 s. Each lesion was dilated once or several times until successful angioplasty was obtained. A successful angioplasty was defined as a stenosis reduction of > 20% with residual stenosis of =< 50%.
25
Electrocardiographic
study
After the recording of a control electrocardiogram, 12-lead electrocardiograms were continuously recorded starting just before the commencement of balloon inflation and terminating 2 min after deflation. The ST segment shift from the baseline was measured 0.16 s after the beginning of QRS complex with hand-held calipers by two observers blinded to our study, because the magnitude of alternans was most marked at this point in our patients. The criterion for marked ST alternans was the presence of an alternate, beat-to-beat change in magnitude of 2 2 mm, shape or form of the ST segment. We examined the time course of ST segment changes during the first coronary occlusion in the lead that showed a maximal ST elevation. Clinical
and angiographic
study
Previous myocardial infarction was diagnosed by typical ischemic chest pain of > 60 min with new Q wave evolution and/or significant elevation of serum creatine kinase. In order to study the history of angina for which the stenosis of the left anterior descending coronary artery was responsible, the duration of the disease was examined only in patients with single-vessel disease of the left anterior descending coronary artery or in those with multivessel disease who had the most severe stenosis in the left anterior descending coronary artery. Coronary angiography was performed in multiprojections including cranially and caudally angulated views. The minimal luminal diameter of each lesion was measured as a percentage of the nearest normal arterial segment with hand-held calipers by three experienced angiographers. The result was expressed as the mean percentage diameter narrowing of two available views. Significant vessel disease was defined as more than 50% luminal diameter stenosis. We defined lesions of the left anterior descending coronary artery before the first large septal perforator as proximal and beyond it as distal. In each patient, we examined the possible involvement of a side branch (i.e. septal and diagonal branches) defined as a
branch in which a transient occlusion occurred during balloon inflation. Grade 2 or more collaterals as defined by Rentrop et al. [21] were considered significant in this study. Statistical
methods
Comparisons of continuous data between the three groups were made with analysis of variance and a multiple comparison method. A paired f-test was used for ST segment changes in Group 1 patients. Group comparisons were made using the chi-square test or Fisher’s exact test for categorical data. Continuous values were expressed as the mean *SD. Results were considered significant at a probability (p) value < 0.05. Results Incidence
of marked ST alternans
A total of 117 balloon inflations were performed in 41 patients. Mean duration of the inflation was 77 _t 18 s, ranging from 60 to 130 s. Eleven (27%) of the 41 patients showed marked ST alternans during coronary angioplasty. ST alternans was observed in 17 (15%) of 117 coronary occlusions. In these 11 patients, ST alternans occurred in 17 (65%) of 26 coronary occlusions. On the first coronary occlusion, ST alternans appeared in all 11 patients, on the second coronary occlusion in 4 (57%) of 7 patients who underwent 2 inflations, and on the third coronary occlusion in 2 (40%) of 5 patients who underwent 3 inflations. However, ST alternans was not observed on the fourth coronary occlusion in 2 patients who underwent 4 inflations, nor on the fifth coronary occlusion in one patient who underwent 5 inflations. The duration of coronary occlusions was 83 f 14 s for the first inflation, 71 ? 12 s for the second inflation and 68 i 11 s for the third inflation. There were no significant differences in the duration of balloon inflation. Observation
of ST alternans
Fig. 1 shows a representative electrocardiogram of a patient in Group 1. We examined the
sion, the ST segments showed a distinct elevation. Marked ST alternans appeared 47 k 22 s after the start of coronary occlusion. The elevation of the ST segment was 7.6 f 2.6 mm just before the appearance of ST alternans. Immediately after the appearance of ST alternans, the elevation of the higher ST segment was 9.0 f 3.4 mm and that of the lower ST segment was 6.7 k 3.0 mm. Then the elevation of the higher ST segment gradually increased and reached a maximum of 14.4 + 5.8 mm just before balloon deflation, whereas the lower ST segment showed no significant change with a value of 8.0 k 3.9 mm before balloon deflation. The difference between the higher and lower ST elevations became more evident during coronary occlusion. ST alternans continued for 39 &-19 s until balloon deflation, when it disappeared rapidly. We examined the time course of ST segment during the second and third coronary occlusion in Group 1. The time from the start of inflation to the onset of marked ST alternans tended to be longer in the second or third coronary occlusion than in the first. The elevation of the higher and
-**7-*-
-**7-**-
20
I
1
Fig. 1. Electrocardiograms (lead V4) recorded during the first balloon inflation in a patient with angina pectoris. A, control electrocardiogram. B and C, electrocardiograms recorded just before balloon inflation and 20 s after balloon inflation. D, ST alternans which appeared 44 s after balloon inflation (black arrow). E, F and G, electrocardiograms recorded 60, 70 and 80 s after balloon inflation. The elevation of the higher ST segment increases progressively but that of the lower ST segment does not increase. H, disappearance of ST alternans (black arrow) after balloon deflation (white arrow).
Time
time course of ST segment changes during the coronary occlusion in Group 1 (Fig. 2). The leads which showed maximal ST elevation were V3 in 3, V4 in 7 and V5 in 1 patient. The level of the ST segments was almost isoelectric in the control state, but it was 2.8 -t 1.9 mm just before coronary occlusion. After the start of coronary occlu-
of
measurement
Fig. 2. Time course of ST segment changes and ST alternans during the first balloon inflation in Group 1 patients. The upper (lower) line between T3 and T7 shows ST levels of a beat with higher (lower) ST elevation. Tl: control, T2: just before balloon inflation, T3: just before the appearance of ST alternans. T4: just after the appearance of ST alternans. T5: mid-course of ST alternans, T6: just before balloon deflation, T7: when ST alternans disappeared. * p < 0.05, * * p < 0.01.
27
TABLE
1
Comparison
of clinical
characteristics
among
Clinical
the three
groups
characteristics
Group 1 (n = 11)
Group 2 (11 = 15)
Group 3 tn = 15)
Age (yr) Male/female Effort angina Rest angina Effort and rest angina
58 + 10 11/o 2 4 5
61 k 11 9/6 * 9 1 5
58 * 19 13/2 11 1 3
4.7 * 2.0 (n = 6) 0
10.8 * 7.3 * (n = 10) 0
5.9 + 3.2 (fl = 15) 15
Duration of angina
of history (mth)
Previous
MI in the LAD area
* p < 0.05 vs Group
1. MI = myocardial
infarction;
LAD = left anterior
coronary
artery.
coronary arterial area was significantly lower in the 11 patients of Group 1 than in the 30 patients of Groups 2 and 3 (0% vs 50%; p < 0.01). We also compared the angiographic data of the three groups (Table 2). There were no significant differences between the groups in the number of diseased vessels, the ratio of proximal/ distal lesions of the left anterior descending coronary artery as a target for coronary angioplasty, the ratio of septal branch/diagonal branch as an involved side branch during angioplasty, the incidence of collateral flow before angioplasty, or duration of coronary occlusion. However, the percentage of stenosis of the target lesion before
lower ST segments varied between the first and following coronary occlusions. Comparison of clinical, angiographic and electrocardiographic data among three groups
We compared the clinical data of the three groups (Table 1). There were no significant differences among the three groups in mean age, incidence of angina at rest or during effort. However, the history of angina in Group 1 was significantly shorter than in Group 2 (4.7 + 2.0 vs 10.8 + 7.3; p < 0.05). The incidence of previous myocardial infarction in the left anterior descending
TABLE
descending
2
Comparison
of angiographic
Angiographic
characteristics
characteristics
Number of diseased vessels Percent stenosis before PTCA Location of stenosis proximal distal Involved side branch septal branch diagonal branch Collateral before PTCA absent present Number of inflations Duration of inflation ts)
* p < 0.01, * * p < 0.001 vs Group
among
the three
groups
Group 1 (n = 11)
Group 2 (n = 15)
Group 3 (n = 15)
1.6 + 62 +
1.7 + 0.8 72 *11*
1.3 + 0.6 81 * 16 **
0.7 5
5
9 6
9 6
7 9
11 10
12 11
15 0 2.x i 1.3 85 * 20
14 1 3.3 + 1.9 86 k 35
6
11 0 2.4 + 1.4 83 *14 1. PTCA = percutaneous
transluminal
coronary
angioplasty
78
IO
0
Control
Tame
Fig. 3. Comparison
after
inflation
20
During the first coronary occlusion, ventricular premature complexes occurred in 6 (58%) of the 11 patients in Group 1, in 2 (13%) of the 15 patients in Group 2 and in 2 (13%) of the 15 patients in Group 3. The differences of incidence between Group 1 patients and Group 2 and 3 patients were statistically significant ( p < 0.05). Moreover, the ventricular arrhythmias of Group 1 included single ventricular premature complexes in 2, ventricular couplets in 2, multifocal ventricular premature complexes in 1 and a run of 8 ventricular premature complexes in 1 patient; whereas all the ventricular arrhythmias of Groups 2 and 3 were single ventricular premature complexes.
30
(set)
of ST elevation of Group Groups 2 and 3. * p < 0.01.
1 with that of
Discussion
coronary angioplasty in Group 1 was significantly lower than in Group 2 or 3 (62 f 5 vs 72 + 11; p < 0.01, vs 81 + 16; p < 0.001). We then examined the extent and time course of ST segment change during the first coronary occlusion among the three groups (Table 3 and Fig. 3). The number of electrocardiographic leads which showed ST elevation during coronary occlusion was significantly greater in Group 1 than in Group 2 or 3 (6.1 k 0.8 vs 5.2 f 1.0 or 5.3 k 1.0; p < 0.05).The ST segment in Group 1 before alternans occurred was significantly higher than the ST segment in Group 2 or 3 at lo,20 and 30 s after coronary occlusion. There were no significant differences in the elevation of the ST segment between Groups 2 and 3 throughout balloon occlusion.
TABLE
Compared with Group 2 and 3 patients, Group 1 patients showed (1) a shorter history of angina, (2) less severe stenosis of the target lesion before coronary angioplasty, (3) more leads showing ST elevation during coronary artery occlusion, (4) higher ST elevation during occlusion and (5) lower incidence of previous myocardial infarction in the left anterior descending coronary arterial area. These characteristics may collectively be considered associated factors of ST alternans during coronary angioplasty. Since the severity of epicardial ST segment elevation is an index of the severity of myocardial ischemia [25], it is possible
3
Comparison
of the extent
Extent and time course ST segment elevation Number
Associated factors of ST alternans
and time course
of
of ST segment
elevation
among
the three
groups.
Group 1 fn = 11)
Group 2 (n = 1.5)
Group 3 (n = 15)
6.1 k 0.8
5.2 k 0.8 *
5.3 + 1.0 *
0.2 2.8 4.3 5.6 6.1
0.9 * 1.6 i 2.4 k 3.5 f 4.0+
0.7 f 1.6 + 2.1 * 3.4 * 4.3*
of leads
with ST elevation Magnitude of ST elevation control just before at 10s at 20 s at 30 s * p < 0.05,
inflation
* * p < 0.01 vs Group
+ + + f +
1.1 1.9 1.8 1.9 1.7 +
1. ’ Two patients
had already
0.5 1.0 1.1 ** 1.5 ** 1.7 **
shown ST alternans
0.6 1.0 1.0 ** 1.2 ** 1.1 **
at 30 s and were excluded
from the analysis.
79
that Group 1 patients, who showed higher ST elevation, had more severe myocardial ischemia induced by acute occlusion of the coronary artery. In 1985, Rentrop et al. [21] studied collateral channel filling immediately after coronary artery occlusion using contralateral dye injection in patients who had undergone coronary angioplasty, and reported that, in a high percent of patients with severe coronary stenosis, collateral channel filling improved within 60 to 90 s after sudden coronary occlusion. In a subsequent study, Rentrop et al. [26] suggested that patients with > 70% stenosis were likely to have some collateral flow after sudden coronary occlusion. Recently, Cohen et al. [27] found that lesion stenosis was the best predictor of collateral reserve. Therefore, compared to Group 2 and 3 patients, Group 1 patients who have had less severe stenosis before angioplasty may have less collateral channel filling immediately after coronary artery occlusion and may have had more severe ischemia during occlusion. This hypothesis is further supported by the observation that there was a progressive increase in the number of large-scale anastomoses with increasing duration of angina1 history in a series of 59 hearts examined post mortem [28]. Group 1 patients had more leads showing ST elevation during coronary occlusion, indicating that more extensive myocardial ischemia was induced in the left anterior descending coronary arterial area. They also had a lower incidence of previous myocardial infarction in that area. In contrast, none of the Group 3 patients, who had had previous myocardial infarction in the left anterior descending coronary arterial area, showed ST alternans. The presence of previous myocardial infarction indicates that the mass of viable myocardium in which acute and severe ischemia can be induced by coronary artery occlusion may be smaller in this area. This loss of viable myocardium would cause an insufficient ischemic area to record ST alternans on surface electrocardiogram during coronary occlusion, and thus may explain the absence of ST alternans in Group 3 patients. It is also possible that well developed coronary collateral vessels, which may be demonstrable within 2 weeks after acute myocardial infarction
[29], may preserve the viable myocardium so that severe ischemia cannot be induced by coronary occlusion. Thus, compared to Group 3 patients, Group 1 patients seem to have more severe and extensive myocardial ischemia due to scarcity of collateral vessels and due to insufficient mass of viable myocardium such as to become ischemic. In addition to these associated factors, the apparent incidence of ST alternans may depend upon the method of detection. We defined marked ST alternans as beat-to-beat change of 2 mm or more. We should indicate that there were more subtle degrees of ST segment alternans as in Fig. 1 in panel D preceding the arrow. This fact cannot be disregarded but we think that this has no influence on the results of this study. It has been demonstrated that the intracoronary electrocardiogram is a more sensitive and reliable indication of local ischemia than surface electrocardiogram [30]. Ekmekci et al. [31] described the phenomenon of paradoxical increase in R-wave amplitude. There were some patients with this phenomenon in our study, but we could not find any correlation between the relative increase in R-wave amplitude and the appearance of ST alternans. Several theories have been proposed to explain ST alternans induced by coronary artery occlusion, including changes in the intracellular action potential [ 16,17,19] and alteration of slow inward calcium current [lg]. However the underlying mechanism of ST alternans is still unknown. Our data provide no explanation for the underlying mechanism but have shown the associated factors of ST alternans in coronary angioplasty.
Compqrison
with ST alternans
in variant
angina
Previous studies [lo-121 have shown that ST alternans in variant angina has the following characteristics: (1) incidence of 14-38% of episodes of ST elevation, (2) occurrence during occlusion phase and disappearance during reperfusion phase, (3) appearance in association with higher elevation and longer duration of ST elevation of ischemic attack, and (41 appearance as precursor of ventricular arrhythmias which occur
30
in 78-100% of patients showing ST alternans during ischemic attack. Our study showed that ST alternans during coronary occlusion by balloon inflation had similar characteristics, such as a latent period after the start of balloon occlusion and association with higher ST elevation. The fact that the major coronary artery is occluded completely and acutely may explain the similarity between ST alternans during episodes of variant angina and during coronary occlusion by balloon inflation in coronary angioplasty. However, ST alternans during coronary angioplasty has a lower incidence of ventricular arrhythmias and more rapid disappearance after balloon deflation. The former may be partly explained by the shorter duration of ischemia induced and the latter by faster reperfusion with rapid balloon deflation. Comparison studies
with ST alternans
in experimental
Our clinical study has had experimental counterparts in which ST alternans has been observed during an occlusion of the coronary artery of animals. The incidence of ST alternans in such experimental studies has been reported to be 89-100% [1,2]. This higher incidence may be due to experimental conditions in which epicardial electrograms as well as surface electrocardiograms were taken during acute coronary artery occlusion in anesthetized open-chest dogs. The longer duration of the occlusion in dogs may be another reason. Previous experimental studies showed that repeated coronary occlusions enhanced the development of ST alternans in dogs [I]. This is in contrast to our results in which the incidence of ST alternans decreased progressively from the first to the following occlusions. This difference in the nature of ST alternans between the first and following occlusions may be related to the preceding balloon inflation, which resulted in transient myocardial ischemia, restoration of coronary flow, changes in the degree of reactive hyperemia [22] and changes in the collateral filling [23]. Recently, Deutsch et al. [24] have reported that an initial 90-s period of coronary occlusion during coronary angioplasty signifi-
cantly influences the clinical, metabolic, and hemodynamic responses to a subsequent occlusion. The lessened ischemic response during the second inflation is accompanied by a decrease in cardiac vein flow (ischemic pre-conditioning), This applies to our finding that ST alternans was observed more frequently in the first inflation than in the following inflations. Clinical
implications
The results of this study have clinical implications for the performing of coronary angioplasty. The appearance of ST alternans may presage the occurrence of ventricular arrhythmias including serious arrhythmias during coronary occlusion by balloon inflation. In a patient who has a shorter history of angina pectoris and a less severe stenosis of the target lesion of angioplasty, ST alternans would be more likely to occur during coronary occlusion. If ST alternans does not occur on the first coronary occlusion, it will probably not occur on the following occlusion, and even if ST alternans occurs on the first occlusion, it may not recur on the following occlusion. The associated factors in coronary angioplasty may also be applicable to variant angina, and the characteristic features of ST alternans in our study may be helpful for understanding the nature of ST alternans in variant angina. Limitations
ST segment changes induced by coronary occlusion occur in many sites, but in this study, occlusion was limited to the left anterior descending coronary artery. The results obtained should not be extended to patients undergoing occlusion of the right or left circumflex coronary artery. We have completely occluded the left anterior descending coronary artery for 77 f 18 s in these patients. In clinical situations in which occlusion of the coronary artery is of longer duration the occurrence and time course of ST alternans would not necessarily be similar to those obtained in this study, because the main determinant of ST alternans of surface electrocardiogram in acute coronary occlusion seems to be the severity and
31
extent of acute myocardial ischemia as discussed above. In some patients studied, we noted ST segment elevation just before the start of inflation. This may show that myocardial ischemia was induced when a deflated balloon catheter was on the stenotic lesion. We started inflation of the balloon just after it was positioned appropriately on the target lesion. Immediately after the start of inflation, the ST segment suddenly showed an additional and distinct elevation. This observation probably indicates that severe ischemia was induced by balloon inflation. Just after balloon deflation, ST ahernans disappeared and ST elevation decreased suddenly. It thus seems reasonable to think that the balloon deflation caused abrupt improvement of severe myocardial ischcmia. It would be important to take this into consideration when interpreting the incidence and time course of ST alternans obtained in our study. All the patients continued administration of Ca antagonist before coronary angioplasty. Hashimoto and Nakashima [ 181 examined the effects of Ca antagonists on the relationship between alternate changes in the ST-T complex of the epicardial electrogram and associated excitationconduction abnormalities during coronary occlusion in anesthetized dogs. They found that verapamil and diltiazem inhibited ST-T alternans and the associated excitation and conduction abnormalities. Therefore the incidence of ST alternans in our study may be underestimated.
6
7 8 Y
IO II
I2
13
14 15
Conclusion We have clarified for the first time the clinical background and electrocardiographic features of marked ST alternans during acute coronary occlusion of the left anterior descending coronary artery. We conclude that ST alternans recorded by surface electrocardiogram may be a marker of acute severe and extensive ischemia of the myocardium.
16
I7
I8
References I Hellerstein HK. Liebow IM. Electrical alternation perimental coronary artery occlusion. Am J 1950; 160:366-374.
in exPhysiol
19
Nakashima M, Hashimoto H. Kanamaru M. Nagaya T, Hashizume M, Oishi H. Experimental studies and clinical report on the electrical alternans of ST segment during myocardial ischemia. Jpn Heart J 1978;19:396-408. Levine HD, Wanzer SH, Merrill JP. Dialyzable currents of injury in potassium, intoxication resembling acute myocardial infarction or pericarditis. Circulation 1956;13:29-36. Rosen IL. ECG of the month. Current Med Dialogue, March 1966: p. 370. Puletti M, Curione M, Righetti G, Jacobellis G. Alternans of the ST segment and T wave in acute myocdrdial infarction. J Electrocardiology 1980;13:297-300. Demidowich G, Werres R, Rothfeld R, Becker J. Electrical alternans of the ST segment in non-Prinzmetal‘s angina. Pace 1980;3:733-736. Wayne VS. Bishop RL, Spodick DH. Exercise-induced ST segment alternans. Chest 1983;83:824-825. Ring ME, Fenster PE. Exercise-induced ST segment alternans. Am Heart J 1986;111:1009-101 I. Williams RR. Wagner GS. Peter RH. ST segment alternans in Prinzmetal’s angina. A report of two cases. Ann Intern Med 1974;81:51-54. Kleinfeld MJ. Rozanski JJ. Alternans of the ST segment in Prinzmetal’s angina. Circulation 1977;55:574-577. Rozanski JJ, Kleinfeld M. Alternans of the ST segment and T wave. A sign of electrical instability in Prinzmetal’s angina. Pace 1982;5:359-365. Turitto G. El-Sherif N. Alternans of the ST segment in variant angina. Incidence, time course and relation to ventricular arrhythmias during ambulatory electrocardiographic recording. Chest 1988;93:587-59 1. Joyal M, Feldman RL, Pepine CJ. ST-segment alternans during percutaneous transluminal coronary angioplasty. Am J Cardiol 1984:54:915-936. Kleinfeld M, Stein E. Electrical alternans of components of action potential. Am Heart J 1968:75:528530. Kleber AG, Janse MJ, Van Capelle FJL, Durrer D. Mechanism and time course of ST and T-Q segment changes during acute regional myocardial &hernia in the pig heart determined by extracellular and intracellular recordings, Cir Res 1978;42:603-613. Russell DC. Smith HJ. Oliver MF. Transmrmbrane potential changes and ventricular fibrillation during repetitive myocardial ischaemia in the dog. Br Heart J 1979;42:88-96. Cinca J. Janse MJ, Morena H, Candell J. Valle V, Durrer D. Mechanism and time course of the early electrical changes during acute coronary artery occlusion. An attempt to correlate the early ECG changes in man to the cellular electrophysiology in the pig. Chest 19X0:77:499505. Hashimoto H, Suzuki K, Miyake S, Nakashima M. Effects of calcium antagonists on the electrical alternans of the ST segment and on associated mechanical alternans during acute coronary occlusion in dogs. Circulation 1983;68:667672. Carson DL, Cardinal R, Savard P, Vermeulen M. Characterization of unipolar waveform alternation in acutely is-
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20
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22
23
24
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chaemic porcine myocardium. Cardiovasc Res 1986;20: 521-527. Smith JM, Clancy EA, Valeri CR, Ruskin JN. Cohen RJ. Electrical alternans and cardiac electrical instability. Circulation 1988;77:110-121. Rentrop KP, Cohen M, Blanke H, Phillips RA. Changes in collateral channel filling immediately after control coronary artery occlusion by an angioplasty balloon in human subjects. J Am Coll Cardiol 1985;5:587-592. Serruys PW, Juilliere Y, Zijlstra F et al. Coronary blood flow velocity during percutaneous transluminal coronary angioplasty as a guide for assessment of the functional result. Am J Cardiol 1988;61:253-259. Hill JA, Feldman RL, MacDonald RG, Pepine CJ. Coronary artery collateral visualization during acute coronary occlusion. Am J Cardiol 1985;55:1216-1218. Deutsch E, Berger M. Kussmaul WG. Hirshfeld WJ, Herrmann CH, Laskey KW. Adaptation to ischemia during percutaneous transluminal coronary angioplasty. Circulation 1990;82:2044-2051. Maroko PR, Kjekshus JK. Sobel BE et al. Factors influencing infarct size following experimental coronary artery occlusion. Circulation 1971:43:67-82.
26 Rentrop KP, Thornton JC. Feit F. Buskirk MV. Determinants and protective potential of coronary arterial collaterals as assessed by an angioplasty model. Am J Cardiol 1988;61:677-684. 27 Cohen M, Sherman W, Rentrop KP, Gorlin R. Determinants of collateral filling observed during sudden controlled coronary artery occlusion in human subjects. J Am Coll Cardiol 1989;13:297-303. 28 Fulton WFM. The time factor in the enlargement of anastomoses in coronary artery disease. Scot Med J 1964:9:18-23. 29 Schwartz H, Leiboff RH, Bren GB et al. Temporal evolution of the human coronary collateral circulation after myocardial infarction. J Am Coll Cardiol 1984;4:10881093. 30 Friedman PL, Shook TL, Kirshenbaum JM, Selwyn AP, Ganz P. Value of the intracoronary electrocardiogram to monitor myocardial ischemia during percutaneous transluminal coronary angioplasty. Circulation 1986:74:330-339. 31 Ekmekci A, Toyoshima H, Kwoczyanski KJ, Nagaya T. Prinzmetal M. Giant R and receding S wave in myocardial ischemia and certain nonischemic conditions. Am J Cardiol 1961;7:521-532.
23
CARD10 01526
Marked alternans of the elevated ST segment during occlusion of the left anterior descending coronary artery in percutaneous transluminal coronary angioplasty: clinical background and electrocardiographic features Hideki Okino, Shin-ichi Arima, Hiroshi Yamaguchi, Shoichiro Nakao and Hiromitsu Tanaka First Department of Internal Medicine, Faculty of Medicine, Kagoshima Utkersity, Kagoshima, Japan
(Received 7 June 1991; revision accepted 7 May 1992)
Okino H, Arima S, Yamaguchi H, Nakao S, Tanaka H. Marked alternans of the elevated ST segment during occlusion of the left anterior descending coronary artery in percutaneous transluminal coronary angioplasty: clinical background and electrocardiographic features. Int J Cardiol 1992;37:23-32. To investigate the clinical background and the electrocardiographic features of marked alternans of the elevated ST segment during coronary angioplasty, we examined 1Zlead electrocardiograms recorded continuously during occlusion of the left anterior descending coronary artery by balloon inflation in 41 patients. The incidence of marked ST alternans was 27% of 41 patients and 15% of 117 balloon occlusions. The incidence decreased progressively from the first to the third occlusion. The time course of ST alternans was determined. Compared with patients without ST alternans, patients with ST alternans had a shorter history of angina, less severe stenosis of the target lesion before coronary angioplasty, more leads showing ST elevation during occlusion, higher ST elevation during occlusion and lower incidence of previous myocardial infarction in the left anterior descending coronary arterial area. ST alternans recorded on the surface electrocardiogram may thus be considered a marker of acute severe and extensive myocardial ischemia. Key words: Acute severe ischemia; Ventricular
arrhythmia; Variant angina; Ca antagonist
Introduction Although alternans of the elevated ST segment in electrocardiography has been observed in
Correspondence to: Hiromitsu Tanaka, M.D., First Department of Internal Medicine, Faculty of Medicine, Kagoshima University. Sakuragaoka 8-3.5-1, Kagoshima City. 890, Japan. Tel. 0992-64-2211, ext. 2137 or 2130.
various conditions [l-13], its occurrence is mostly related to severe myocardial ischemia. Since Hellerstein and Liebow [ll reported that electrical alternans including ST alternans was frequently observed following occlusion of the left anterior descending coronary artery, several investigators [ 14-201 have performed experimental studies on the nature and underlying mechanism of ST alternans induced by severe myocardial ischemia.
24
Clinically, ST alternans has also been observed in variant angina. In 1977, Kleinfeld and Rozanski 1101reported that alternans of the ST segment was found in 8 of 21 patients (38%) of Prinzmetal’s variant angina and that it was an electrocardiographic sign in the surface electrocardiogram reflecting an unstable electrical state of the myocardium. In 1982, Rosanski and Kleinfeld [ll] showed that the occurrence of alternans of the ST segment and T wave frequently heralded the onset of ventricular arrhythmias in Prinzmetal’s angina. Recently, Turitto and El-Sherif [12] demonstrated that alternans of the ST segment represented an index of the severity of ischemia and a precursor of ventricular arrhythmias in variant angina. Percutaneous transluminal coronary angioplasty seems to provide a useful model for studying the effects of acute coronary occlusion by balloon inflation during routine therapeutic intervention. In 1984, Joyal et al. [13] reported that ST-segment alternans was observed during coronary angioplasty in a patient with exertional angina. However, to our knowledge, no systematic study has been made of ST alternans during coronary angioplasty. In the present clinical model, measurement of the duration of balloon inflation, localization of the site of coronary artery occluded by the balloon, angiographic data including coronary anatomy and electrocardiographic data were obtained for the study of ST alternans induced by coronary artery occlusion. The present study was undertaken (1) to delineate the electrocardiographic features of marked ST alternans during balloon occlusion of the left anterior descending coronary artery, and (2) to clarify the clinical background to ST alternans in acute coronary occlusion.
Materials
and Methods
Patients Among 130 consecutive patients who underwent their first angioplasty in our department, we selected 41 consecutive patients in whom the left anterior descending coronary artery was a target
for coronary angioplasty and in whom a significant magnitude of ST elevation was observed during coronary occlusion. ST elevation 12 mm 0.16 s after the beginning of QRS complex was defined to be significant. Patients with the following characteristics were excluded: (1) atria1 fibrillation, (2) acute myocardial infarction, (3) acute coronary occlusion occurring during coronary angioplasty, and (4) right or left bundle branch block. The 41 patients ranged in age from 33 to 78 with a mean of 59 yr. There were 33 males and 8 females. We classified the patients into three groups. Group 1 consisted of 11 patients who showed ST alternans during coronary occlusion. Group 2 consisted of 15 patients without previous myocardial infarction in the left anterior descending coronary arterial area who showed no ST alternans. Group 3 consisted of 15 patients with previous myocardial infarction in the left anterior descending coronary arterial area who showed no ST alternans. None of the Group 1 patients had had previous myocardial infarction in the area. Coronary angioplasty protocol Routine antianginal medication consisting of long-acting nitrates, calcium antagonists (diltiazem 90-120 mg daily or nifedipine 20-40 mg daily) and anti-platelet drugs (aspirin 80 mg daily and dipyridamole 150 mg daily) were continued. Nitroglycerine (0.3-0.5 pg/kg/min) and low molecular weight dextran (100 ml/h) were given by intravenous infusion starting 2 h before the procedure. Immediately before control coronary angiography, heparin (10,000 units) was administered intravenously and isosorbide dinitrate (2.55.0 mg> was selectively injected into the coronary artery as a bolus. Coronary angioplasty was performed from the femoral approach using the standard technique. Dilatation was performed with an appropriately sized Simpson-Robert dilatation balloon catheter (ACS) for 60-130 s. Each lesion was dilated once or several times until successful angioplasty was obtained. A successful angioplasty was defined as a stenosis reduction of > 20% with residual stenosis of =< 50%.
25
Electrocardiographic
study
After the recording of a control electrocardiogram, 12-lead electrocardiograms were continuously recorded starting just before the commencement of balloon inflation and terminating 2 min after deflation. The ST segment shift from the baseline was measured 0.16 s after the beginning of QRS complex with hand-held calipers by two observers blinded to our study, because the magnitude of alternans was most marked at this point in our patients. The criterion for marked ST alternans was the presence of an alternate, beat-to-beat change in magnitude of 2 2 mm, shape or form of the ST segment. We examined the time course of ST segment changes during the first coronary occlusion in the lead that showed a maximal ST elevation. Clinical
and angiographic
study
Previous myocardial infarction was diagnosed by typical ischemic chest pain of > 60 min with new Q wave evolution and/or significant elevation of serum creatine kinase. In order to study the history of angina for which the stenosis of the left anterior descending coronary artery was responsible, the duration of the disease was examined only in patients with single-vessel disease of the left anterior descending coronary artery or in those with multivessel disease who had the most severe stenosis in the left anterior descending coronary artery. Coronary angiography was performed in multiprojections including cranially and caudally angulated views. The minimal luminal diameter of each lesion was measured as a percentage of the nearest normal arterial segment with hand-held calipers by three experienced angiographers. The result was expressed as the mean percentage diameter narrowing of two available views. Significant vessel disease was defined as more than 50% luminal diameter stenosis. We defined lesions of the left anterior descending coronary artery before the first large septal perforator as proximal and beyond it as distal. In each patient, we examined the possible involvement of a side branch (i.e. septal and diagonal branches) defined as a
branch in which a transient occlusion occurred during balloon inflation. Grade 2 or more collaterals as defined by Rentrop et al. [21] were considered significant in this study. Statistical
methods
Comparisons of continuous data between the three groups were made with analysis of variance and a multiple comparison method. A paired f-test was used for ST segment changes in Group 1 patients. Group comparisons were made using the chi-square test or Fisher’s exact test for categorical data. Continuous values were expressed as the mean *SD. Results were considered significant at a probability (p) value < 0.05. Results Incidence
of marked ST alternans
A total of 117 balloon inflations were performed in 41 patients. Mean duration of the inflation was 77 _t 18 s, ranging from 60 to 130 s. Eleven (27%) of the 41 patients showed marked ST alternans during coronary angioplasty. ST alternans was observed in 17 (15%) of 117 coronary occlusions. In these 11 patients, ST alternans occurred in 17 (65%) of 26 coronary occlusions. On the first coronary occlusion, ST alternans appeared in all 11 patients, on the second coronary occlusion in 4 (57%) of 7 patients who underwent 2 inflations, and on the third coronary occlusion in 2 (40%) of 5 patients who underwent 3 inflations. However, ST alternans was not observed on the fourth coronary occlusion in 2 patients who underwent 4 inflations, nor on the fifth coronary occlusion in one patient who underwent 5 inflations. The duration of coronary occlusions was 83 f 14 s for the first inflation, 71 ? 12 s for the second inflation and 68 i 11 s for the third inflation. There were no significant differences in the duration of balloon inflation. Observation
of ST alternans
Fig. 1 shows a representative electrocardiogram of a patient in Group 1. We examined the
sion, the ST segments showed a distinct elevation. Marked ST alternans appeared 47 k 22 s after the start of coronary occlusion. The elevation of the ST segment was 7.6 f 2.6 mm just before the appearance of ST alternans. Immediately after the appearance of ST alternans, the elevation of the higher ST segment was 9.0 f 3.4 mm and that of the lower ST segment was 6.7 k 3.0 mm. Then the elevation of the higher ST segment gradually increased and reached a maximum of 14.4 + 5.8 mm just before balloon deflation, whereas the lower ST segment showed no significant change with a value of 8.0 k 3.9 mm before balloon deflation. The difference between the higher and lower ST elevations became more evident during coronary occlusion. ST alternans continued for 39 &-19 s until balloon deflation, when it disappeared rapidly. We examined the time course of ST segment during the second and third coronary occlusion in Group 1. The time from the start of inflation to the onset of marked ST alternans tended to be longer in the second or third coronary occlusion than in the first. The elevation of the higher and
-**7-*-
-**7-**-
20
I
1
Fig. 1. Electrocardiograms (lead V4) recorded during the first balloon inflation in a patient with angina pectoris. A, control electrocardiogram. B and C, electrocardiograms recorded just before balloon inflation and 20 s after balloon inflation. D, ST alternans which appeared 44 s after balloon inflation (black arrow). E, F and G, electrocardiograms recorded 60, 70 and 80 s after balloon inflation. The elevation of the higher ST segment increases progressively but that of the lower ST segment does not increase. H, disappearance of ST alternans (black arrow) after balloon deflation (white arrow).
Time
time course of ST segment changes during the coronary occlusion in Group 1 (Fig. 2). The leads which showed maximal ST elevation were V3 in 3, V4 in 7 and V5 in 1 patient. The level of the ST segments was almost isoelectric in the control state, but it was 2.8 -t 1.9 mm just before coronary occlusion. After the start of coronary occlu-
of
measurement
Fig. 2. Time course of ST segment changes and ST alternans during the first balloon inflation in Group 1 patients. The upper (lower) line between T3 and T7 shows ST levels of a beat with higher (lower) ST elevation. Tl: control, T2: just before balloon inflation, T3: just before the appearance of ST alternans. T4: just after the appearance of ST alternans. T5: mid-course of ST alternans, T6: just before balloon deflation, T7: when ST alternans disappeared. * p < 0.05, * * p < 0.01.
27
TABLE
1
Comparison
of clinical
characteristics
among
Clinical
the three
groups
characteristics
Group 1 (n = 11)
Group 2 (11 = 15)
Group 3 tn = 15)
Age (yr) Male/female Effort angina Rest angina Effort and rest angina
58 + 10 11/o 2 4 5
61 k 11 9/6 * 9 1 5
58 * 19 13/2 11 1 3
4.7 * 2.0 (n = 6) 0
10.8 * 7.3 * (n = 10) 0
5.9 + 3.2 (fl = 15) 15
Duration of angina
of history (mth)
Previous
MI in the LAD area
* p < 0.05 vs Group
1. MI = myocardial
infarction;
LAD = left anterior
coronary
artery.
coronary arterial area was significantly lower in the 11 patients of Group 1 than in the 30 patients of Groups 2 and 3 (0% vs 50%; p < 0.01). We also compared the angiographic data of the three groups (Table 2). There were no significant differences between the groups in the number of diseased vessels, the ratio of proximal/ distal lesions of the left anterior descending coronary artery as a target for coronary angioplasty, the ratio of septal branch/diagonal branch as an involved side branch during angioplasty, the incidence of collateral flow before angioplasty, or duration of coronary occlusion. However, the percentage of stenosis of the target lesion before
lower ST segments varied between the first and following coronary occlusions. Comparison of clinical, angiographic and electrocardiographic data among three groups
We compared the clinical data of the three groups (Table 1). There were no significant differences among the three groups in mean age, incidence of angina at rest or during effort. However, the history of angina in Group 1 was significantly shorter than in Group 2 (4.7 + 2.0 vs 10.8 + 7.3; p < 0.05). The incidence of previous myocardial infarction in the left anterior descending
TABLE
descending
2
Comparison
of angiographic
Angiographic
characteristics
characteristics
Number of diseased vessels Percent stenosis before PTCA Location of stenosis proximal distal Involved side branch septal branch diagonal branch Collateral before PTCA absent present Number of inflations Duration of inflation ts)
* p < 0.01, * * p < 0.001 vs Group
among
the three
groups
Group 1 (n = 11)
Group 2 (n = 15)
Group 3 (n = 15)
1.6 + 62 +
1.7 + 0.8 72 *11*
1.3 + 0.6 81 * 16 **
0.7 5
5
9 6
9 6
7 9
11 10
12 11
15 0 2.x i 1.3 85 * 20
14 1 3.3 + 1.9 86 k 35
6
11 0 2.4 + 1.4 83 *14 1. PTCA = percutaneous
transluminal
coronary
angioplasty
78
IO
0
Control
Tame
Fig. 3. Comparison
after
inflation
20
During the first coronary occlusion, ventricular premature complexes occurred in 6 (58%) of the 11 patients in Group 1, in 2 (13%) of the 15 patients in Group 2 and in 2 (13%) of the 15 patients in Group 3. The differences of incidence between Group 1 patients and Group 2 and 3 patients were statistically significant ( p < 0.05). Moreover, the ventricular arrhythmias of Group 1 included single ventricular premature complexes in 2, ventricular couplets in 2, multifocal ventricular premature complexes in 1 and a run of 8 ventricular premature complexes in 1 patient; whereas all the ventricular arrhythmias of Groups 2 and 3 were single ventricular premature complexes.
30
(set)
of ST elevation of Group Groups 2 and 3. * p < 0.01.
1 with that of
Discussion
coronary angioplasty in Group 1 was significantly lower than in Group 2 or 3 (62 f 5 vs 72 + 11; p < 0.01, vs 81 + 16; p < 0.001). We then examined the extent and time course of ST segment change during the first coronary occlusion among the three groups (Table 3 and Fig. 3). The number of electrocardiographic leads which showed ST elevation during coronary occlusion was significantly greater in Group 1 than in Group 2 or 3 (6.1 k 0.8 vs 5.2 f 1.0 or 5.3 k 1.0; p < 0.05).The ST segment in Group 1 before alternans occurred was significantly higher than the ST segment in Group 2 or 3 at lo,20 and 30 s after coronary occlusion. There were no significant differences in the elevation of the ST segment between Groups 2 and 3 throughout balloon occlusion.
TABLE
Compared with Group 2 and 3 patients, Group 1 patients showed (1) a shorter history of angina, (2) less severe stenosis of the target lesion before coronary angioplasty, (3) more leads showing ST elevation during coronary artery occlusion, (4) higher ST elevation during occlusion and (5) lower incidence of previous myocardial infarction in the left anterior descending coronary arterial area. These characteristics may collectively be considered associated factors of ST alternans during coronary angioplasty. Since the severity of epicardial ST segment elevation is an index of the severity of myocardial ischemia [25], it is possible
3
Comparison
of the extent
Extent and time course ST segment elevation Number
Associated factors of ST alternans
and time course
of
of ST segment
elevation
among
the three
groups.
Group 1 fn = 11)
Group 2 (n = 1.5)
Group 3 (n = 15)
6.1 k 0.8
5.2 k 0.8 *
5.3 + 1.0 *
0.2 2.8 4.3 5.6 6.1
0.9 * 1.6 i 2.4 k 3.5 f 4.0+
0.7 f 1.6 + 2.1 * 3.4 * 4.3*
of leads
with ST elevation Magnitude of ST elevation control just before at 10s at 20 s at 30 s * p < 0.05,
inflation
* * p < 0.01 vs Group
+ + + f +
1.1 1.9 1.8 1.9 1.7 +
1. ’ Two patients
had already
0.5 1.0 1.1 ** 1.5 ** 1.7 **
shown ST alternans
0.6 1.0 1.0 ** 1.2 ** 1.1 **
at 30 s and were excluded
from the analysis.
79
that Group 1 patients, who showed higher ST elevation, had more severe myocardial ischemia induced by acute occlusion of the coronary artery. In 1985, Rentrop et al. [21] studied collateral channel filling immediately after coronary artery occlusion using contralateral dye injection in patients who had undergone coronary angioplasty, and reported that, in a high percent of patients with severe coronary stenosis, collateral channel filling improved within 60 to 90 s after sudden coronary occlusion. In a subsequent study, Rentrop et al. [26] suggested that patients with > 70% stenosis were likely to have some collateral flow after sudden coronary occlusion. Recently, Cohen et al. [27] found that lesion stenosis was the best predictor of collateral reserve. Therefore, compared to Group 2 and 3 patients, Group 1 patients who have had less severe stenosis before angioplasty may have less collateral channel filling immediately after coronary artery occlusion and may have had more severe ischemia during occlusion. This hypothesis is further supported by the observation that there was a progressive increase in the number of large-scale anastomoses with increasing duration of angina1 history in a series of 59 hearts examined post mortem [28]. Group 1 patients had more leads showing ST elevation during coronary occlusion, indicating that more extensive myocardial ischemia was induced in the left anterior descending coronary arterial area. They also had a lower incidence of previous myocardial infarction in that area. In contrast, none of the Group 3 patients, who had had previous myocardial infarction in the left anterior descending coronary arterial area, showed ST alternans. The presence of previous myocardial infarction indicates that the mass of viable myocardium in which acute and severe ischemia can be induced by coronary artery occlusion may be smaller in this area. This loss of viable myocardium would cause an insufficient ischemic area to record ST alternans on surface electrocardiogram during coronary occlusion, and thus may explain the absence of ST alternans in Group 3 patients. It is also possible that well developed coronary collateral vessels, which may be demonstrable within 2 weeks after acute myocardial infarction
[29], may preserve the viable myocardium so that severe ischemia cannot be induced by coronary occlusion. Thus, compared to Group 3 patients, Group 1 patients seem to have more severe and extensive myocardial ischemia due to scarcity of collateral vessels and due to insufficient mass of viable myocardium such as to become ischemic. In addition to these associated factors, the apparent incidence of ST alternans may depend upon the method of detection. We defined marked ST alternans as beat-to-beat change of 2 mm or more. We should indicate that there were more subtle degrees of ST segment alternans as in Fig. 1 in panel D preceding the arrow. This fact cannot be disregarded but we think that this has no influence on the results of this study. It has been demonstrated that the intracoronary electrocardiogram is a more sensitive and reliable indication of local ischemia than surface electrocardiogram [30]. Ekmekci et al. [31] described the phenomenon of paradoxical increase in R-wave amplitude. There were some patients with this phenomenon in our study, but we could not find any correlation between the relative increase in R-wave amplitude and the appearance of ST alternans. Several theories have been proposed to explain ST alternans induced by coronary artery occlusion, including changes in the intracellular action potential [ 16,17,19] and alteration of slow inward calcium current [lg]. However the underlying mechanism of ST alternans is still unknown. Our data provide no explanation for the underlying mechanism but have shown the associated factors of ST alternans in coronary angioplasty.
Compqrison
with ST alternans
in variant
angina
Previous studies [lo-121 have shown that ST alternans in variant angina has the following characteristics: (1) incidence of 14-38% of episodes of ST elevation, (2) occurrence during occlusion phase and disappearance during reperfusion phase, (3) appearance in association with higher elevation and longer duration of ST elevation of ischemic attack, and (41 appearance as precursor of ventricular arrhythmias which occur
30
in 78-100% of patients showing ST alternans during ischemic attack. Our study showed that ST alternans during coronary occlusion by balloon inflation had similar characteristics, such as a latent period after the start of balloon occlusion and association with higher ST elevation. The fact that the major coronary artery is occluded completely and acutely may explain the similarity between ST alternans during episodes of variant angina and during coronary occlusion by balloon inflation in coronary angioplasty. However, ST alternans during coronary angioplasty has a lower incidence of ventricular arrhythmias and more rapid disappearance after balloon deflation. The former may be partly explained by the shorter duration of ischemia induced and the latter by faster reperfusion with rapid balloon deflation. Comparison studies
with ST alternans
in experimental
Our clinical study has had experimental counterparts in which ST alternans has been observed during an occlusion of the coronary artery of animals. The incidence of ST alternans in such experimental studies has been reported to be 89-100% [1,2]. This higher incidence may be due to experimental conditions in which epicardial electrograms as well as surface electrocardiograms were taken during acute coronary artery occlusion in anesthetized open-chest dogs. The longer duration of the occlusion in dogs may be another reason. Previous experimental studies showed that repeated coronary occlusions enhanced the development of ST alternans in dogs [I]. This is in contrast to our results in which the incidence of ST alternans decreased progressively from the first to the following occlusions. This difference in the nature of ST alternans between the first and following occlusions may be related to the preceding balloon inflation, which resulted in transient myocardial ischemia, restoration of coronary flow, changes in the degree of reactive hyperemia [22] and changes in the collateral filling [23]. Recently, Deutsch et al. [24] have reported that an initial 90-s period of coronary occlusion during coronary angioplasty signifi-
cantly influences the clinical, metabolic, and hemodynamic responses to a subsequent occlusion. The lessened ischemic response during the second inflation is accompanied by a decrease in cardiac vein flow (ischemic pre-conditioning), This applies to our finding that ST alternans was observed more frequently in the first inflation than in the following inflations. Clinical
implications
The results of this study have clinical implications for the performing of coronary angioplasty. The appearance of ST alternans may presage the occurrence of ventricular arrhythmias including serious arrhythmias during coronary occlusion by balloon inflation. In a patient who has a shorter history of angina pectoris and a less severe stenosis of the target lesion of angioplasty, ST alternans would be more likely to occur during coronary occlusion. If ST alternans does not occur on the first coronary occlusion, it will probably not occur on the following occlusion, and even if ST alternans occurs on the first occlusion, it may not recur on the following occlusion. The associated factors in coronary angioplasty may also be applicable to variant angina, and the characteristic features of ST alternans in our study may be helpful for understanding the nature of ST alternans in variant angina. Limitations
ST segment changes induced by coronary occlusion occur in many sites, but in this study, occlusion was limited to the left anterior descending coronary artery. The results obtained should not be extended to patients undergoing occlusion of the right or left circumflex coronary artery. We have completely occluded the left anterior descending coronary artery for 77 f 18 s in these patients. In clinical situations in which occlusion of the coronary artery is of longer duration the occurrence and time course of ST alternans would not necessarily be similar to those obtained in this study, because the main determinant of ST alternans of surface electrocardiogram in acute coronary occlusion seems to be the severity and
31
extent of acute myocardial ischemia as discussed above. In some patients studied, we noted ST segment elevation just before the start of inflation. This may show that myocardial ischemia was induced when a deflated balloon catheter was on the stenotic lesion. We started inflation of the balloon just after it was positioned appropriately on the target lesion. Immediately after the start of inflation, the ST segment suddenly showed an additional and distinct elevation. This observation probably indicates that severe ischemia was induced by balloon inflation. Just after balloon deflation, ST ahernans disappeared and ST elevation decreased suddenly. It thus seems reasonable to think that the balloon deflation caused abrupt improvement of severe myocardial ischcmia. It would be important to take this into consideration when interpreting the incidence and time course of ST alternans obtained in our study. All the patients continued administration of Ca antagonist before coronary angioplasty. Hashimoto and Nakashima [ 181 examined the effects of Ca antagonists on the relationship between alternate changes in the ST-T complex of the epicardial electrogram and associated excitationconduction abnormalities during coronary occlusion in anesthetized dogs. They found that verapamil and diltiazem inhibited ST-T alternans and the associated excitation and conduction abnormalities. Therefore the incidence of ST alternans in our study may be underestimated.
6
7 8 Y
IO II
I2
13
14 15
Conclusion We have clarified for the first time the clinical background and electrocardiographic features of marked ST alternans during acute coronary occlusion of the left anterior descending coronary artery. We conclude that ST alternans recorded by surface electrocardiogram may be a marker of acute severe and extensive ischemia of the myocardium.
16
I7
I8
References I Hellerstein HK. Liebow IM. Electrical alternation perimental coronary artery occlusion. Am J 1950; 160:366-374.
in exPhysiol
19
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